About 8% of the human genome consists of sequences classified as Human endogenous retroviruses (HERVs), which are remnants of ancient retroviral integrations in the human genome. HERV elements have degenerated over millions of years of evolution and most of them can no longer encode complete proteins, let alone produce infectious viral particles, due to the accumulation of mutations, deletions, and/or truncations. Despite the fact that HERVs had integrated into the human genome millions of year ago, some HERV genes still have open reading frames (ORFs) and thus can potentially code for protein.
HERV-W expression has been detected in lung, gastric, ovarian and bladder cancers, and HERV-W has been reported to induce Vβ16 biased T cell response when presented as “multiple sclerosis retroviral particles.” These observations are in line with previous findings on a mouse model for germinal center (GC)-derived B cell lymphomas. In this SJL mouse model, the lymphomas arise as a result of transcription of a retroviral superantigen (vSAg29) encoded for by an endogenous mouse mammary tumor virus (mtv29). The vSAg29 vigorously stimulates TCR Vβ16+CD4+ T cells, which in turn elaborate copious amounts of growth-promoting cytokines upon which the lymphoma cells depend for their growth. This phenomenon has been characterized as reverse immune surveillance.
Furthermore, an examination of CD4 T cells obtained from diffuse large B cell lymphomas (DLCL), representing a major class of non-Hodgkin's lymphomas, revealed the presence of oligoclonal TCR BV families based on their non-Gaussian distribution of CDR3 lengths, when compared to normal lymph node CD4 T cells. In addition, the representation of the TCRBV families among the CD4+ T cells was skewed. One clear example is a case in which such CD4 T cells were followed in two stages of lymphoma development in a patient. Lymphoma-host CD4 T cell interaction was observed in which the lymphoma cells stimulated syngeneic response in PBL CD4 T cells, resulting in BV23 oligoclonality (92% of BV23 had the same CDR3 length as observed for the lymphoma-containing CD4 T cells).
Human cancers are a significant health problem in the United States and throughout the world. Although advances have been made in detection and treatment of the disease, there remains a need for additional means of detection and treatment of cancer.